Villejuif/ Paris, June 20th 2017
Discovery of a new mechanism involved in the migration of cancer cells
Cell migration is a normal process which is essential to life. In oncology it is involved in the formation of new metastases.
“Up till the present, we knew that the cell relied on certain structures to anchor itself within its environment. We have now identified new cell structures known as ‘clathrin-coated pits’, already known to be important for other cell functions. The cancer cell uses them as hooks to attach to other structures in order to move around, These novel structures underlie some 50% of cell adhesion to surrounding structures,” declared Guillaume Montagnac, Leader of the ATIP-Avenir team, attached to Inserm Unit 1170, “Normal and abnormal haematopoiesis”, at Gustave Roussy.
Recognised in 1964, these clathrin pits are small invaginations of the cell membrane which allow it to renew itself or to help molecules to enter the cells. The cell uses them particularly to supply itself with nutritional material (iron, cholesterol, etc.).
Using fluorescence methods, the researchers succeeded in demonstrating with an aggressive human breast cancer line, known for its marked propensity to metastasise, that the clathrin pits adhere to collagen fibres and surround them. The pit squeezes the fibre, so strengthening its hold and allowing it to move.
“Our Gustave Roussy team is one of the few with an interest in cell membrane dynamics when the cell is placed in 3D matrices under conditions close to normal ones. By studying these clathrin pits in 3D we were able to see the phenomenon when we were not expecting it,” concluded Guillaume Montagnac.
A breast cancer cell with actin (engine of migration) in red, the clathrin pits (cell hooks) in green and collagen fibres in blue.
Tubular clathrin/AP-2 lattices pinch collagen fibers to support 3D cell migration
Nadia Elkhatib1, Enzo Bresteau1, Francesco Baschieri1, Alba López Rioja1, Guillaume van Niel2, Stéphane Vassilopoulos3, Guillaume Montagnac1
1Inserm U1170, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
2Institut Curie, UMR144, Université de Recherche Paris Sciences et Lettres, Centre Universitaire, Paris, France à l’époque des travaux, actuellement à l’hôpital Sainte-Anne, Center of Psychiatry and Neurosciences, U894 Inserm, Paris, France.
3Inserm/Université Pierre et Marie Curie UMR S974, Institut de Myologie, Paris, France.